SRN1 Mechanism in Heteroaromatic Nucleophilic Substitution. Reactions Involving Halogenated Pyrimidines, Pyridazines, and Pyrazines

Article abstract of DOI:10.1021/jo00315a013

Reactions of 2-chloropyrimidine (1), 4-chloro-2,6-dimethoxypyrimidine (7), 3-chloro-6-methoxypyridazine (9), and 2-chloropyrazine (14) with a representative series of ketone enolates in liquid ammonia exhibited characteristics consistent with a radical-chain (S_RN1) mechanism for substituton.Diazines 1 and 9 showed an unexpected sensitivity to enolate ion structure, with 1 reacting best with tertiary enolates and 9 undergoing substitution most satisfactorily with primary enolates.The order of S_RN1 reactivity among the various substrates was found to be 14 > 9 > 7 =ca. 1.Thus 1 and 7 required photostimulation at 35o nm for satisfactory displacemement of chloride, 9 underwent some substitution without illumination, and 14 reacted smoothly in the dark.